Histocompatibility (or transplantation) antigens are cell components that were originally detected because of the immunity which they elicit upon transplantation of tissues and cells. More recently it has been recognized that the histocompatibility genes have other biological significance, as evidenced in man by the association of histocompatibility antigen phenotype and incidence of specific malignancies and in rodents by susceptibility to oncogenic viruses, development of immunocompetence and resistance to maternal-fetal interactions. Cellular antigens of the rat, particularly those involved in histocompatability reaction, are being studied by genetic and serological procedures to expand the usefulness of this species for immunological, biochemical and genetic studies of cell differentiation. A multiple-allergic locus (Ag-B) determining potent histocompatability antigens has been defined, and the complexity of the serological specificities in different strains is being analyzed by cytotoxic antibody tests. In addition, the distributions of these and other serologically detectable rat antigens are being studied in normal adult, embryonic and tumor tissues to provide a basis for understanding their biological properties and significance. The distribution among rat populations of antigens determined by two histocompatibility loci is influenced by maternal-fetal interactions, presumably of immunological origin. These are being analyzed for evidence of mechanisms which operate against the well-being and longevity of progeny of particular antigen phenotypes. Presumably these may be the same pressures which predispose individuals of particular antigen phenotype towards susceptibility to various disease states, including selected kinds of carcinogenesis.